Lentiviruses are non-oncogenic retroviruses that cause persistent infection and chronic disease after prolonged inoculation periods. The viruses include the human immunodeficiency viruses (HIV) and simian immunodeficiency viruses (SIV) as well as lentiviruses of Feline, Bovine and Equine species and the ungulate lentiviruses. Lentiviruses cause two types of disease; immunodeficiency disease as a result of loss of helper T lymphocytes and organ specific disease in brain, lung and intestine associated with replication in macrophages. HIV (in adults) and SIV cause both types of disease, pediatric AIDS is characterized by more organ specific disease, and the ungulate lentiviruses (visna virus and caprine arthritis encephalitis virus, CAEV) cause only the organ specific disease. The target cell for the immunodeficiency viruses is CD4 lymphocytes as well as macrophages. However, the ungulate lentivirus, visna virus and CAEV, target the monocyte/macrophages. The receptor for the immunodeficiency viruses is the CD4 molecule on lymphocytes, but the receptor for the macrophage tropic lentiviruses has not been identified. Visna virus binds to a molecule on virus susceptible cells. Antibody to this 5OkD surface protein specifically blocks the binding of visna virus to cells. These data provide the basis for isolation of molecular clones of the visna virus receptor. Molecular cloning of the receptor will allow the characterization of the receptor molecule and identification of it in target organs. Characterization of the receptor for the ungulate lentiviruses will provide a molecular tool to understand the basis for the organ specific disease caused by these viruses and may provide leads to understanding how the immunodeficiency virus cause organ specific disease.